Freek Polak vs Yoram Stein – BNR 9 april 2010
Cannabinoids 2008;3(4):11-15 (corrected 10 December 2008)
© International Association for Cannabis as Medicine 11
Mini-review
Cannabinoids and schizophrenia: where is the
link?
Kirsten Müller-Vahl
Clinic of Psychiatry, Socialpsychiatry & Psychotherapy, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover,
Germany
Abstract
Highlighting the association between schizophrenia and cannabis sativa and the endogenous can-
nabinoid receptor system, respectively, two opposite aspects are of major relevance. On the one
hand, there is substantial evidence that cannabis has to be classified as an independent risk factor
for psychosis that may lead to a worse outcome of the disease. This risk seems to be increased in
genetically predisposed people and may depend on the amount of cannabis used. On the other
hand, there are several lines of evidence suggesting that, at least in a subgroup of patients, altera-
tions in the endocannabinoid system may contribute to the pathogenesis of schizophrenia, e.g., in-
creased density of cannabinoid receptor type 1 (CB1) binding and increased levels of cerebrospinal
fluid (CSF) anandamide. Accordingly, beside the „dopamine hypothesis“ of schizophrenia a „can-
nabinoid hypothesis“ has been suggested. Interestingly, there is a complex interaction between the
dopaminergic and the cannabinoid receptor system. Thus, agents that interact with the cannabinoid
receptor system such as the non-psychoactive cannabidiol (CBD) have been suggested for the
treatment of psychosis.
Keywords: Cannabis, THC, tetrahydrocannabinol, schizophrenia, psychosis
This article can be downloaded, printed and distributed freely for any non-commercial purposes, provided the original work is prop-
erly cited (see copyright info below). Available online at www.cannabis-med.org
Author's address: Kirsten Müller-Vahl, mueller-vahl.kirsten@mh-hannover.de
Introduction
Schizophrenia is a common psychiatric disorder char-
acterized by impairments in the perception or expres-
sion of reality. Schizophrenic symptoms are sub-
classified into positive (or productive) symptoms such
as delusions, auditory hallucinations, and thought dis-
order, and negative (or deficit) symptoms such as
blunted affect and emotion, poverty of speech, anhedo-
nia, and lack of motivation. For many patients the
prognosis is poor with incomplete recovery and signifi-
cant illness. A multifactorial pathogenesis is assumed
including genetic and environmental factors, neurobio-
logical alterations, as well as psychological and social
processes. Pathophysiologically there is evidence for
an alteration in the dopaminergic system with increased
dopaminergic activity in subcortical areas including the
striatum, and decreased dopaminergic activity in corti-
cal areas such as the prefrontal cortex. Dopamine re-
ceptor antagonists (neuroleptics) are the first choice
treatment in schizophrenia.
Within the brain an endogenous cannabinoid system
has been detected including different receptors (mainly
the cannabinoid-1-receptor (CB1)) as well as a series
of lipophilic endogenous ligands and enzymes for the
biosynthesis and degradation of these endocannbinoids.
CB1 receptors inhibit the release of several neuro-
transmitters and neuromodulators including dopamine,
GABA, serotonine, glutamate, noradrenaline, and ace-
tylcholine. The two most important endocannabinoids
are anandamide (N-arachidonylethanolamide, AEA)
and 2-arachidonoyl glycerol (2-AG). While 2-AG is a
full agonist at the cannabinoid receptor, anandamide is
a partial agonist, However, anandamide, in addition, is
a full agonist at the vanilloid (VR1) receptor.
Cannabis as a risk factor for psychosis
The relationship between schizophrenia and the use of
cannabinoids is complex and not completely under-
stood. While it is well established that high doses of
cannabis can cause a transient toxic psychosis, it is
Mini-review
12 Cannabinoids Vol 3, No 4 November 9, 2008
unclear whether cannabis use increases the risk of
psychotic illness persisting after abstinence from the
drug. However, there is substantial evidence that heavy
cannabis abuse in healthy persons is a risk factor for
the clinical manifestation of schizophrenia and triggers
both the onset of psychotic episodes in predisposed
individuals and the relapse in patients with schizophre-
nia. Since the vast majority of cannabis users do not
develop psychosis, it can be hypothesized that some
people are genetically vulnerable to these effects of
cannabis.
In the general population, it has been shown that can-
nabis negatively impact cognitive functioning, al-
though it is unclear whether cognitive deficits even
persist after abstinence for a longer period. Investigat-
ing the effects of cannabis on cognitive functions in
patients with first episode psychosis, it has been dem-
onstrated that cognitive functioning and performance is
comparable or even better (i.e., higher scores for prob-
lem solving and reasoning and visual memory) in those
patients using cannabis compared to non-using patients
[1, 2, 3] suggesting a possible neuroprotective effect of
cannabis among persons with schizophrenia [3].
More recently, several epidemiological studies have
been performed investigating whether cannabis use
acts as an independent risk factor in the onset of
schizophrenia. A large cohort study with more than
50.000 subjects found that heavy cannabis use at age
18 increases the risk for later schizophrenia six-fold
compared to non-users suggesting a causal relationship
between cannabis use and an increased risk of develop-
ing schizophrenia [4, 5]. In addition, not only a dose-
response relation between cumulative exposure to
cannabis use and the psychosis outcome [4, 6] could be
demonstrated, but also an age dependence with in-
creased likelihood for adult-onset schizophreniform
disorder after early use (by age 15) compared to later
cannabis use (by age 18) [6, 7]. Moreover, individuals
with an established vulnerability to psychotic disorder
seem to have a markedly worse outcome when using
cannabis [6, 8, 9, 10, 11].
Interaction between the dopaminergic and the
cannabinoid system
There is a large number of both animal and human
studies available substantiating an interaction between
the cannabinoid and the dopaminergic system. Since it
has been suggested that psychosis is caused by an
overactive dopaminergic system (the „dopamine hy-
pothesis“ of schizophrenia) [12], it has been speculated
that cannabinoids might cause or exacerbate psychoses
by increasing the activity of the dopaminergic system.
There are several lines of evidence suggesting that in
patients with cannabis-induced psychosis a genetic
vulnerability may lead to an increased dopaminergic
activity [13]. In dopamine transporter (DAT) knockout
(KO) mice, an animal model associated with hyper-
dopaminergia that has been suggested to be relevant to
schizophrenia, a significant decrease of striatal anan-
damide levels has been demonstrated further suggest-
ing that hyperdopaminergia leads to alterations of the
cannabinoid system [14].
The “cannabinoid hypothesis”of schizophrenia
The hypothesis that the consumption of exogenous
cannabinoids may contribute to the pathophysiology of
psychosis is further supported by observations in
healthy volunteers because administration of intrave-
nous delta-9-tetrahydrocannabinol (THC) to healthy
individuals may produce transient schizophrenia-like
positive and negative symptoms [15, 16, 17, 18].
The binocular depth inversion test (BDIT) can be used
as a model of illusionary visual perception. Using the
BDIT to investigate cognitive impairment in patients
with schizophrenia, it could be demonstrated that pa-
tients with schizophrenia are more veridical in their
judgments viewing inverted (concave) faces [19].
However, this impaired binocular depth inversion im-
proved in parallel to clinically effective antipsychotic
treatment [20]. In healthy volunteers, it can be assumed
that cognitive factors override the binocular disparity
cues of stereopsis and, thereby, correct an implausible
perceptual hypothesis. Accordingly, it has been sug-
gested that impairment of binocular depth inversion
reflects a common final pathway, characterized by an
impairment of adaptive systems regulating perception
[21].
Investigating binocular depth inversion in THC-
intoxicated normal volunteers compared to both
healthy controls and patients suffering from productive
psychoses, similar alterations were detected in THC-
intoxicated normal volunteers and patients with
schizophrenia [19]. Therefore, comparable distur-
bances in the internal regulation of perceptual proc-
esses in patients with schizophrenia and THC-
intoxicated people can be assumed suggesting that a
dysfunctional cannabinoid receptor system might un-
derlie at least a subtype of endogenous psychoses [19].
An involvement of the cannabinoid receptor system in
schizophrenia is further supported by findings in cere-
brospinal fluid (CSF) in patients with schizophrenia.
The CSF concentrations of the endocannabinoids an-
andamide and palmitylethanolamide (PEA) were found
significantly increased in patients with schizophrenia
compared to non-schizophrenic controls. Therefore, it
has been suggested that changes in the endocannabi-
noid concentrations in schizophrenia might reflect
either a homeostatic adaption of the cannabinoid sys-
tem to a primary dopaminergic dysfunction or a pri-
mary „hypercannabinergic“ state [22]. In addition, CSF
anandamide levels were found eight-fold higher in
antipsychotic-näive patients with first-episode paranoid
schizophrenia than in healthy controls [23]. Because in
non-medicated patients with acute schizophrenia CSF
anandamide levels were negatively correlated with
psychotic symptoms, it has been hypothesized that
anandamide elevation in acute paranoid schizophrenia
may reflect a compensatory adaptation to the disease
Müller-Vahl
Cannabinoids Vol 3, No 4 November 9, 2008 13
state [23]. While frequent cannabis exposure may
down-regulate anandamide signaling in the brain of
patients with schizophrenia, but not of healthy indi-
viduals, it can be speculated that frequent cannabis use
increases the risk for psychotic episodes only in those
individuals who exhibit preexisting pathologically
hyperactive anandamide levels, as demonstrated in
patients with first episode schizophrenia [24].
There is only a limited number of investigations avail-
able measuring endocannabinoid levels in plasma in
patients with schizophrenia demonstrating increased
amounts of both anandamide and the mRNA for the
anandamide degrading enzyme fatty acid amide hy-
drolase (FAAH) in patients with schizophrenia [25,
26]. Successful antipsychotic treatment led to a reduc-
tion of anandamide blood levels and of the mRNA
transcripts for cannabinoid receptors type 2 (CB2) and
FAAH [25]. 2-arachidonoyl glycerol (2-AG) levels
were found significantly lower in neuroleptic-näive
patients with first-episode schizophrenia compared to
patients with chronic schizophrenia after withdrawal
from neuroleptic medication. Based on these findings it
has been suggested that an increase in plasma anan-
damide levels might be related to the disease independ-
ently of the state, but 2-AG might be related to disease
progression [26].
With regard to a cannabinoid hypothesis of schizo-
phrenia, it is of importance that highest densities of
cannabinoid receptors type 1 (CB1) in the brain are
found in those regions that have been implicated in
schizophrenia, including the prefrontal cortex, basal
ganglia, hippocampus, and the anterior cingulate cortex
(ACC). In postmortem studies CB1 receptor binding
density was found to be increased in the dorsolateral
prefrontal cortex and in the posterior cingulate cortex
(PCC) in patients with schizophrenia. At present results
regarding the ACC remain contradictory [27, 28].
These data, however, demonstrated for the first time
alterations in CB1 receptor binding in patients with
schizophrenia.
Neuroimaging studies of the CB1 receptor
In vivo neuroimaging using positron emission tomo-
graphy (PET) and single photon emission computed
tomography (SPECT) to investigate different aspects of
the cannabinoid CB1 receptor system is in a very pre-
liminary state. To date, there is only one single case
study available investigating a patient with schizophre-
nia that demonstrates a high cannabinoid CB1 receptor
binding in the striatum and the pallidum, and a moder-
ately high binding in the frontal cortex, the temporal
cortex and the cerebellum. These findings reflect re-
sults from in vitro studies regarding receptor distribu-
tion [29].
From several magnetic resonance imaging (MRI) stud-
ies it is known that patients with schizophrenia have
progressive brain reductions [30, 31]. By contrast,
volumetric MRI studies in („healthy“) cannabis users
resulted in inconsistent findings with reduced [32] or
normal [33] brain volumes. From recent MRI studies it
is suggested that in patients with schizophrenia canna-
bis use might amplify a pre-existent vulnerability to
brain volume changes [34], in particular in regions rich
in CB1 receptors such as the PCC [35].
Genetic predisposition for cannabis-induced
schizophreniform disorders
Because variants within the cannabinoid receptor gene
(CNR1) (AAT repeat polymorphism) were found to be
associated with schizophrenia, it has been supposed
that the cannabinoid CB1 receptor system is over-
activated in patients with some types of schizophrenia
[36, 37]. Recent studies, in addition, demonstrated that
specific genetic variations (the valine158 allele of the
catechol-O-methyltransferase, COMT) may lead to an
increased risk not only to exhibit psychotic symptoms
but also to develop cannabis-induced schizophreniform
disorders [38]. This effect, however, was observed only
for people using cannabis before the age of 18 for the
first time. From these data a gene x environment inter-
action between COMT genotype and cannabis use on
risk of schizophrenia has been deduced [38].
CBD improves psychotic symptoms
Cannabidiol (CBD) is a major non-psychotropic con-
stituent of cannabis. Case studies [39] as well as a
double-blind controlled study [40] suggested that CBD
may be effective in the treatment of patients suffering
from acute schizophrenia. The endogenous cannabi-
noid system, therefore, has been proposed as a possible
novel therapeutic target for the treatment of acute
schizophrenia [40]. However, the underlying patho-
physiological mechanisms of CBD in schizophrenia
remain unclear.
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http://www.cannabis-med.org/english/nav/home-
conference.htm.
A more extensive review on this issue is available from
the author:
Müller-Vahl KR, Emrich HM. Cannabis and schizo-
phrenia: towards a cannabinoid hypothesis of schizo-
phrenia. Expert Rev Neurother 2008;8(7):1037-48.
http://www.cannabis-med.org/english/journal/en_2008_04_1.pdf
© International Association for Cannabis as Medicine 11
Mini-review
Cannabinoids and schizophrenia: where is the
link?
Kirsten Müller-Vahl
Clinic of Psychiatry, Socialpsychiatry & Psychotherapy, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover,
Germany
Abstract
Highlighting the association between schizophrenia and cannabis sativa and the endogenous can-
nabinoid receptor system, respectively, two opposite aspects are of major relevance. On the one
hand, there is substantial evidence that cannabis has to be classified as an independent risk factor
for psychosis that may lead to a worse outcome of the disease. This risk seems to be increased in
genetically predisposed people and may depend on the amount of cannabis used. On the other
hand, there are several lines of evidence suggesting that, at least in a subgroup of patients, altera-
tions in the endocannabinoid system may contribute to the pathogenesis of schizophrenia, e.g., in-
creased density of cannabinoid receptor type 1 (CB1) binding and increased levels of cerebrospinal
fluid (CSF) anandamide. Accordingly, beside the „dopamine hypothesis“ of schizophrenia a „can-
nabinoid hypothesis“ has been suggested. Interestingly, there is a complex interaction between the
dopaminergic and the cannabinoid receptor system. Thus, agents that interact with the cannabinoid
receptor system such as the non-psychoactive cannabidiol (CBD) have been suggested for the
treatment of psychosis.
Keywords: Cannabis, THC, tetrahydrocannabinol, schizophrenia, psychosis
This article can be downloaded, printed and distributed freely for any non-commercial purposes, provided the original work is prop-
erly cited (see copyright info below). Available online at www.cannabis-med.org
Author's address: Kirsten Müller-Vahl, mueller-vahl.kirsten@mh-hannover.de
Introduction
Schizophrenia is a common psychiatric disorder char-
acterized by impairments in the perception or expres-
sion of reality. Schizophrenic symptoms are sub-
classified into positive (or productive) symptoms such
as delusions, auditory hallucinations, and thought dis-
order, and negative (or deficit) symptoms such as
blunted affect and emotion, poverty of speech, anhedo-
nia, and lack of motivation. For many patients the
prognosis is poor with incomplete recovery and signifi-
cant illness. A multifactorial pathogenesis is assumed
including genetic and environmental factors, neurobio-
logical alterations, as well as psychological and social
processes. Pathophysiologically there is evidence for
an alteration in the dopaminergic system with increased
dopaminergic activity in subcortical areas including the
striatum, and decreased dopaminergic activity in corti-
cal areas such as the prefrontal cortex. Dopamine re-
ceptor antagonists (neuroleptics) are the first choice
treatment in schizophrenia.
Within the brain an endogenous cannabinoid system
has been detected including different receptors (mainly
the cannabinoid-1-receptor (CB1)) as well as a series
of lipophilic endogenous ligands and enzymes for the
biosynthesis and degradation of these endocannbinoids.
CB1 receptors inhibit the release of several neuro-
transmitters and neuromodulators including dopamine,
GABA, serotonine, glutamate, noradrenaline, and ace-
tylcholine. The two most important endocannabinoids
are anandamide (N-arachidonylethanolamide, AEA)
and 2-arachidonoyl glycerol (2-AG). While 2-AG is a
full agonist at the cannabinoid receptor, anandamide is
a partial agonist, However, anandamide, in addition, is
a full agonist at the vanilloid (VR1) receptor.
Cannabis as a risk factor for psychosis
The relationship between schizophrenia and the use of
cannabinoids is complex and not completely under-
stood. While it is well established that high doses of
cannabis can cause a transient toxic psychosis, it is
Mini-review
12 Cannabinoids Vol 3, No 4 November 9, 2008
unclear whether cannabis use increases the risk of
psychotic illness persisting after abstinence from the
drug. However, there is substantial evidence that heavy
cannabis abuse in healthy persons is a risk factor for
the clinical manifestation of schizophrenia and triggers
both the onset of psychotic episodes in predisposed
individuals and the relapse in patients with schizophre-
nia. Since the vast majority of cannabis users do not
develop psychosis, it can be hypothesized that some
people are genetically vulnerable to these effects of
cannabis.
In the general population, it has been shown that can-
nabis negatively impact cognitive functioning, al-
though it is unclear whether cognitive deficits even
persist after abstinence for a longer period. Investigat-
ing the effects of cannabis on cognitive functions in
patients with first episode psychosis, it has been dem-
onstrated that cognitive functioning and performance is
comparable or even better (i.e., higher scores for prob-
lem solving and reasoning and visual memory) in those
patients using cannabis compared to non-using patients
[1, 2, 3] suggesting a possible neuroprotective effect of
cannabis among persons with schizophrenia [3].
More recently, several epidemiological studies have
been performed investigating whether cannabis use
acts as an independent risk factor in the onset of
schizophrenia. A large cohort study with more than
50.000 subjects found that heavy cannabis use at age
18 increases the risk for later schizophrenia six-fold
compared to non-users suggesting a causal relationship
between cannabis use and an increased risk of develop-
ing schizophrenia [4, 5]. In addition, not only a dose-
response relation between cumulative exposure to
cannabis use and the psychosis outcome [4, 6] could be
demonstrated, but also an age dependence with in-
creased likelihood for adult-onset schizophreniform
disorder after early use (by age 15) compared to later
cannabis use (by age 18) [6, 7]. Moreover, individuals
with an established vulnerability to psychotic disorder
seem to have a markedly worse outcome when using
cannabis [6, 8, 9, 10, 11].
Interaction between the dopaminergic and the
cannabinoid system
There is a large number of both animal and human
studies available substantiating an interaction between
the cannabinoid and the dopaminergic system. Since it
has been suggested that psychosis is caused by an
overactive dopaminergic system (the „dopamine hy-
pothesis“ of schizophrenia) [12], it has been speculated
that cannabinoids might cause or exacerbate psychoses
by increasing the activity of the dopaminergic system.
There are several lines of evidence suggesting that in
patients with cannabis-induced psychosis a genetic
vulnerability may lead to an increased dopaminergic
activity [13]. In dopamine transporter (DAT) knockout
(KO) mice, an animal model associated with hyper-
dopaminergia that has been suggested to be relevant to
schizophrenia, a significant decrease of striatal anan-
damide levels has been demonstrated further suggest-
ing that hyperdopaminergia leads to alterations of the
cannabinoid system [14].
The “cannabinoid hypothesis”of schizophrenia
The hypothesis that the consumption of exogenous
cannabinoids may contribute to the pathophysiology of
psychosis is further supported by observations in
healthy volunteers because administration of intrave-
nous delta-9-tetrahydrocannabinol (THC) to healthy
individuals may produce transient schizophrenia-like
positive and negative symptoms [15, 16, 17, 18].
The binocular depth inversion test (BDIT) can be used
as a model of illusionary visual perception. Using the
BDIT to investigate cognitive impairment in patients
with schizophrenia, it could be demonstrated that pa-
tients with schizophrenia are more veridical in their
judgments viewing inverted (concave) faces [19].
However, this impaired binocular depth inversion im-
proved in parallel to clinically effective antipsychotic
treatment [20]. In healthy volunteers, it can be assumed
that cognitive factors override the binocular disparity
cues of stereopsis and, thereby, correct an implausible
perceptual hypothesis. Accordingly, it has been sug-
gested that impairment of binocular depth inversion
reflects a common final pathway, characterized by an
impairment of adaptive systems regulating perception
[21].
Investigating binocular depth inversion in THC-
intoxicated normal volunteers compared to both
healthy controls and patients suffering from productive
psychoses, similar alterations were detected in THC-
intoxicated normal volunteers and patients with
schizophrenia [19]. Therefore, comparable distur-
bances in the internal regulation of perceptual proc-
esses in patients with schizophrenia and THC-
intoxicated people can be assumed suggesting that a
dysfunctional cannabinoid receptor system might un-
derlie at least a subtype of endogenous psychoses [19].
An involvement of the cannabinoid receptor system in
schizophrenia is further supported by findings in cere-
brospinal fluid (CSF) in patients with schizophrenia.
The CSF concentrations of the endocannabinoids an-
andamide and palmitylethanolamide (PEA) were found
significantly increased in patients with schizophrenia
compared to non-schizophrenic controls. Therefore, it
has been suggested that changes in the endocannabi-
noid concentrations in schizophrenia might reflect
either a homeostatic adaption of the cannabinoid sys-
tem to a primary dopaminergic dysfunction or a pri-
mary „hypercannabinergic“ state [22]. In addition, CSF
anandamide levels were found eight-fold higher in
antipsychotic-näive patients with first-episode paranoid
schizophrenia than in healthy controls [23]. Because in
non-medicated patients with acute schizophrenia CSF
anandamide levels were negatively correlated with
psychotic symptoms, it has been hypothesized that
anandamide elevation in acute paranoid schizophrenia
may reflect a compensatory adaptation to the disease
Müller-Vahl
Cannabinoids Vol 3, No 4 November 9, 2008 13
state [23]. While frequent cannabis exposure may
down-regulate anandamide signaling in the brain of
patients with schizophrenia, but not of healthy indi-
viduals, it can be speculated that frequent cannabis use
increases the risk for psychotic episodes only in those
individuals who exhibit preexisting pathologically
hyperactive anandamide levels, as demonstrated in
patients with first episode schizophrenia [24].
There is only a limited number of investigations avail-
able measuring endocannabinoid levels in plasma in
patients with schizophrenia demonstrating increased
amounts of both anandamide and the mRNA for the
anandamide degrading enzyme fatty acid amide hy-
drolase (FAAH) in patients with schizophrenia [25,
26]. Successful antipsychotic treatment led to a reduc-
tion of anandamide blood levels and of the mRNA
transcripts for cannabinoid receptors type 2 (CB2) and
FAAH [25]. 2-arachidonoyl glycerol (2-AG) levels
were found significantly lower in neuroleptic-näive
patients with first-episode schizophrenia compared to
patients with chronic schizophrenia after withdrawal
from neuroleptic medication. Based on these findings it
has been suggested that an increase in plasma anan-
damide levels might be related to the disease independ-
ently of the state, but 2-AG might be related to disease
progression [26].
With regard to a cannabinoid hypothesis of schizo-
phrenia, it is of importance that highest densities of
cannabinoid receptors type 1 (CB1) in the brain are
found in those regions that have been implicated in
schizophrenia, including the prefrontal cortex, basal
ganglia, hippocampus, and the anterior cingulate cortex
(ACC). In postmortem studies CB1 receptor binding
density was found to be increased in the dorsolateral
prefrontal cortex and in the posterior cingulate cortex
(PCC) in patients with schizophrenia. At present results
regarding the ACC remain contradictory [27, 28].
These data, however, demonstrated for the first time
alterations in CB1 receptor binding in patients with
schizophrenia.
Neuroimaging studies of the CB1 receptor
In vivo neuroimaging using positron emission tomo-
graphy (PET) and single photon emission computed
tomography (SPECT) to investigate different aspects of
the cannabinoid CB1 receptor system is in a very pre-
liminary state. To date, there is only one single case
study available investigating a patient with schizophre-
nia that demonstrates a high cannabinoid CB1 receptor
binding in the striatum and the pallidum, and a moder-
ately high binding in the frontal cortex, the temporal
cortex and the cerebellum. These findings reflect re-
sults from in vitro studies regarding receptor distribu-
tion [29].
From several magnetic resonance imaging (MRI) stud-
ies it is known that patients with schizophrenia have
progressive brain reductions [30, 31]. By contrast,
volumetric MRI studies in („healthy“) cannabis users
resulted in inconsistent findings with reduced [32] or
normal [33] brain volumes. From recent MRI studies it
is suggested that in patients with schizophrenia canna-
bis use might amplify a pre-existent vulnerability to
brain volume changes [34], in particular in regions rich
in CB1 receptors such as the PCC [35].
Genetic predisposition for cannabis-induced
schizophreniform disorders
Because variants within the cannabinoid receptor gene
(CNR1) (AAT repeat polymorphism) were found to be
associated with schizophrenia, it has been supposed
that the cannabinoid CB1 receptor system is over-
activated in patients with some types of schizophrenia
[36, 37]. Recent studies, in addition, demonstrated that
specific genetic variations (the valine158 allele of the
catechol-O-methyltransferase, COMT) may lead to an
increased risk not only to exhibit psychotic symptoms
but also to develop cannabis-induced schizophreniform
disorders [38]. This effect, however, was observed only
for people using cannabis before the age of 18 for the
first time. From these data a gene x environment inter-
action between COMT genotype and cannabis use on
risk of schizophrenia has been deduced [38].
CBD improves psychotic symptoms
Cannabidiol (CBD) is a major non-psychotropic con-
stituent of cannabis. Case studies [39] as well as a
double-blind controlled study [40] suggested that CBD
may be effective in the treatment of patients suffering
from acute schizophrenia. The endogenous cannabi-
noid system, therefore, has been proposed as a possible
novel therapeutic target for the treatment of acute
schizophrenia [40]. However, the underlying patho-
physiological mechanisms of CBD in schizophrenia
remain unclear.
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A more extensive review on this issue is available from
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http://www.cannabis-med.org/english/journal/en_2008_04_1.pdf
Klik hier voor meer informatie over het Cannabis Tribunaal 2010, met o.a. Gerd Leers, Hans van Duijn, Fred Teeven, Dries van Agt en Freek Polak.
Klik hieronder om het debat te beluisteren:
Freek Polak vs Yoram Stein – BNR 9 april 2010
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